摘要目的 探讨多聚腺苷酸二磷酸核糖聚合酶(PARP)抑制剂3-氨基苯甲酰胺(3-AB)对重症急性胰腺炎(SAP)肺损伤治疗作用的机制.方法 36只Wistar大鼠按随机数字法分为假手术对照组(SO组)、SAP组和3-AB处理组.采用5％牛磺胆酸钠逆行胰胆管注射法制备SAP模型,3-AB组在SAP造模前、后30 min分别经静脉注射3-AB (10 mg/kg).术后12 h测定血清淀粉酶、肺组织湿/干比、肺髓过氧化物酶(MPO)水平,光镜观察胰腺和肺脏病理变化,逆转录-聚合酶链反应法检测肺组织IL-1β和IL-6 mRNA表达,蛋白免疫印迹法检测肺组织TNF-α和ICAM-1蛋白表达.结果 SAP制模后血清淀粉酶、胰腺和肺损伤评分、肺组织湿/干比和MPO值,肺IL-1β和IL-6 mRNA的表达、TNF-α和ICAM-1蛋白表达水平均明显升高(P＜0.05).应用3-AB处理后,上述指标较SAP组均明显下降(P＜0.05).结论 PARP抑制剂3-AB可能通过抑制肺组织MPO,下调IL-1β、IL-6、TNF-α和ICAM-1等炎症介质的表达,对SAP肺损伤发挥保护和治疗作用.

abstractsObjective To investigate the protective effects of poly-ADP-ribose polymerase inhibitor 3-aminobenzamide (3-AB) on lung injury in rats with severe acute pancreatitis (SAP) and to explore the mechanisms.Methods Thirty-six Wistar rats were randomly (random number) divided into three groups (n =12 for each group),namely sham operation (SO) group,SAP group and 3-AB-treated group.The model of SAP-associated lung injury was established by retrograde injection of 5％ sodium taurocholate (STC) into the biliopancreatic duct.In the treated group,3-AB in dose of 10 mg/kg was administered twice by intravenous injection 30 min before and 30 min after STC infusion.The survival rats were sacrificed 12hours after SAP modeling,and the serum amylase,lung wet/dry ratio and myeloperoxidase (MPO) activity were determined,and pathological scores of pancreas and lung tissue were evaluated under light microscope.Expressions of interleukin (IL) -1 β and IL-6 mRNA,tumor necrosis factor α (TNF-α) and inter-cellular adhesion molecule-1 (ICAM-1) protein were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot,respectively. Results The serum amylase level,lung wet/dry ratio and MPO activity,IL-1β and IL-6 mRNA expressions,TNF-α and ICAM-1 protein levels were dramatically increased in SAP group ( P ＜ 0.05 ).Treatment with 3-AB significantly reduced these biomarkers in 3-AB group than in SAP group (P ＜ 0.05 ).Conclusions Poly-ADP-ribose polymerase inhibitor 3-AB exerts the protective and therapeutic effects on lung injury associated with severe acute pancreatitis through inhibiting intrapulmonary MPO activity and down-regulating the expressions of IL-1 β and IL-6 mRNA as well as the levels of TNF-α,and ICAM-1.